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ETFA  -  electron-transfer-flavoprotein, alpha...

Homo sapiens

Synonyms: Alpha-ETF, EMA, Electron transfer flavoprotein subunit alpha, mitochondrial, GA2, MADD
 
 
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Disease relevance of ETFA

 

Psychiatry related information on ETFA

  • The scales showed the highest correlations for the probable Alzheimer's disease patient group (62) (Global Assessment of Dementia; GAD vs. ADL: r = 0.91; Extended Mini-Mental Assessment; EMA vs. GAD: r = 0.91; ADL vs. EMA: r = 0.86) [4].
 

High impact information on ETFA

  • Using [35S]methionine labeling, we also studied the biosynthesis in cultured normal human fibroblasts. p alpha-ETF was detected when the cells were labeled in the presence of dinitrophenol or rhodamine 6G [5].
  • Among six glutaric aciduria type II (GAII) and two ethylmalonic-adipic aciduria cell lines, defective p alpha-ETF synthesis was observed in three GAII cell lines, and beta-ETF synthesis was normal [5].
  • We tried to establish whether the small intestine of CD patients is the site of EMA production and whether gliadin challenge could induce their release [6].
  • GA1 and GA2 showed strong enhancer activity both in a stable transformation assay and in a transient expression assay [2].
  • The HeLa genome contains multiple copies of GA1, while GA2 exists once in the genome [2].
 

Chemical compound and disease context of ETFA

 

Biological context of ETFA

  • The identity of the cDNA clones was further confirmed by matching the amino acid sequence deduced from the nucleotide sequence of the cDNAs to amino acid sequences determined from seven tryptic peptides prepared from purified rat alpha-subunit of electron transfer flavoprotein (alpha-ETF) [11].
  • We used cDNA probes for the Etfdh, Etfb, and Etfa genes to determine localization of these mouse genes to chromosomes 3, 7, and 13 [12].
  • Forty-seven (17%) developed drug resistance to EMA/CO, of whom 33 (70%) were salvaged by further cisplatin-based chemotherapy and surgery [3].
  • This chimeric activator protein, like the mouse protein, is also able to stimulate the hydrolysis of GA2 by HexB [13].
  • In most cells, glycosylation of LacCer, GM3, and GD3 to form higher order species (GA2, GM2, GD2, GM1, GD1b) is displaced toward the most distal aspects of the Golgi and the trans-Golgi network, where the involved transferases (GalNAcT and GalT2) form physical and functional associations [14].
 

Anatomical context of ETFA

  • In our previous study of eight glutaric acidemia type II (GAII) fibroblast lines by using [35S]methionine labeling and immunoprecipitation, three of them had a defect in the synthesis of the alpha-subunit of electron transfer flavoprotein (alpha-ETF) (Ikeda et al. 1986) [15].
  • It was not detected either in two other alpha-ETF-deficient GAII or in seven control cell lines [15].
  • Tumor cell colonies were characterized morphologically by Pappenheim stain and immunologically for surface antigens by peroxidase-antiperoxidase immunostaining utilizing monoclonal antibodies (carcinoembryonic antigen 26/3/13 and 26/5/1, EMA, HEA125, Sam 2 and Sam 10) which detected epithelial cell antigens [16].
  • Postinduction therapy included a second course of EMA in 27 patients, maintenance in 10, autologous bone marrow transplantation (BMT) in 12, and allogeneic BMT in 13 [17].
  • A panel of eight antibodies (Cam 5.2, B72.3, CEA, EMA, MCA, Lewis X, ER, and PR) demonstrate that the squamous, transition zone, duct, acinar, and myoepithelial cells or Bartholin's gland are antigenically distinct, and are similar to those reported in analogous areas of the uterine cervix [18].
 

Associations of ETFA with chemical compounds

  • If serum hCG was < or = 100 IU/L, patients received dactinomycin; if hCG was greater than 100 IU/L, patients received EMA/CO [19].
  • PATIENTS AND METHODS: We report the results of the regimen of mitoxantrone on days 1 to 3, etoposide on days 8 to 10, and cytarabine on days 1 to 3 and 8 to 10 (EMA) in 133 patients, with a median follow-up of 40 months [17].
  • These results provide clear evidence on the existence of an alternative pathway for GM2 catabolism in mice by converting GM2 to GA2 and subsequently to lactosylceramide [20].
  • EMA positivity was associated with an 8% reduction in mean serum cholesterol (0.5 mmol/l; p<0.01) and reductions in mean haemoglobin (0.3 g/dl; p<0.01), total protein (1.0 g/l; p<0.05), and corrected serum calcium (0.02 mmol/l; p<0.05) [21].
  • The EMA86 study showed efficacy of intensive sequential chemotherapy with mitoxantrone, 12 mg/m2 day on days 1-3, etoposide, 200 mg/m2/day as a continuous infusion on days 8-10 and cytarabine (araC), 500 mg/m2/day as continuous infusion on days 1-3 and 8-10 (EMA regimen) in previously treated patients with AML [7].
 

Other interactions of ETFA

  • ETF is a mitochondrial matrix protein consisting of alpha- (30kDa) and beta- (28kDa) subunits encoded by the ETFA and ETFB genes, respectively [22].
 

Analytical, diagnostic and therapeutic context of ETFA

References

  1. In situ polymerase chain reaction-based localization studies support role of human herpesvirus-8 as the cause of two AIDS-related neoplasms: Kaposi's sarcoma and body cavity lymphoma. Foreman, K.E., Bacon, P.E., Hsi, E.D., Nickoloff, B.J. J. Clin. Invest. (1997) [Pubmed]
  2. Random isolation of gene activator elements from the human genome. Hamada, H. Mol. Cell. Biol. (1986) [Pubmed]
  3. EMA/CO for high-risk gestational trophoblastic tumors: results from a cohort of 272 patients. Bower, M., Newlands, E.S., Holden, L., Short, D., Brock, C., Rustin, G.J., Begent, R.H., Bagshawe, K.D. J. Clin. Oncol. (1997) [Pubmed]
  4. Assessing Alzheimer severity with a global clinical scale. Ashford, J.W., Kumar, V., Barringer, M., Becker, M., Bice, J., Ryan, N., Vicari, S. International psychogeriatrics / IPA. (1992) [Pubmed]
  5. Biosynthesis of electron transfer flavoprotein in a cell-free system and in cultured human fibroblasts. Defect in the alpha subunit synthesis is a primary lesion in glutaric aciduria type II. Ikeda, Y., Keese, S.M., Tanaka, K. J. Clin. Invest. (1986) [Pubmed]
  6. Production of antiendomysial antibodies after in-vitro gliadin challenge of small intestine biopsy samples from patients with coeliac disease. Picarelli, A., Maiuri, L., Frate, A., Greco, M., Auricchio, S., Londei, M. Lancet (1996) [Pubmed]
  7. Granulocyte-macrophage colony-stimulating factor (GM-CSF) to increase efficacy of intensive sequential chemotherapy with etoposide, mitoxantrone and cytarabine (EMA) in previously treated acute myeloid leukemia: a multicenter randomized placebo-controlled trial (EMA91 Trial). Thomas, X., Fenaux, P., Dombret, H., Delair, S., Dreyfus, F., Tilly, H., Vekhoff, A., Cony-Makhoul, P., Leblond, V., Troussard, X., Cordonnier, C., de Revel, T., Simon, M., Nicolini, F., Stoppa, A.M., Janvier, M., Bordessoule, D., Rousselot, P., Ffrench, M., Marie, J.P., Archimbaud, E. Leukemia (1999) [Pubmed]
  8. The management of gestational trophoblastic tumors with etoposide, methotrexate, and actinomycin D. Soto-Wright, V., Goldstein, D.P., Bernstein, M.R., Berkowitz, R.S. Gynecol. Oncol. (1997) [Pubmed]
  9. Results with the EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) regimen in high risk gestational trophoblastic tumours, 1979 to 1989. Newlands, E.S., Bagshawe, K.D., Begent, R.H., Rustin, G.J., Holden, L. British journal of obstetrics and gynaecology. (1991) [Pubmed]
  10. Dose-escalation study of single dose mitoxantrone in combination with timed sequential chemotherapy in patients with refractory or relapsing acute myelogenous leukemia. Thomas, X., Cambier, N., Taksin, A.L., Reman, O., Vekhoff, A., Pautas, C., Leblond, V., Soler-Michel, P., Ecstein-Fraïssé, E., Archimbaud, E. Leuk. Res. (2000) [Pubmed]
  11. Molecular cloning and nucleotide sequence of cDNAs encoding the alpha-subunit of human electron transfer flavoprotein. Finocchiaro, G., Ito, M., Ikeda, Y., Tanaka, K. J. Biol. Chem. (1988) [Pubmed]
  12. Assignment of Etfdh, Etfb, and Etfa to chromosomes 3, 7, and 13: the mouse homologs of genes responsible for glutaric acidemia type II in human. White, R.A., Dowler, L.L., Angeloni, S.V., Koeller, D.M. Genomics (1996) [Pubmed]
  13. Catabolism of asialo-GM2 in man and mouse. Specificity of human/mouse chimeric GM2 activator proteins. Bertoni, C., Li, Y.T., Li, S.C. J. Biol. Chem. (1999) [Pubmed]
  14. Ganglioside glycosyltransferases organize in distinct multienzyme complexes in CHO-K1 cells. Giraudo, C.G., Maccioni, H.J. J. Biol. Chem. (2003) [Pubmed]
  15. Molecular characterization of variant alpha-subunit of electron transfer flavoprotein in three patients with glutaric acidemia type II--and identification of glycine substitution for valine-157 in the sequence of the precursor, producing an unstable mature protein in a patient. Indo, Y., Glassberg, R., Yokota, I., Tanaka, K. Am. J. Hum. Genet. (1991) [Pubmed]
  16. Effects of human bone marrow stroma on the growth of human tumor cells. Strobel, E.S., Strobel, H.G., Bross, K.J., Winterhalter, B., Fiebig, H.H., Schildge, J.U., Löhr, G.W. Cancer Res. (1989) [Pubmed]
  17. Timed sequential chemotherapy for previously treated patients with acute myeloid leukemia: long-term follow-up of the etoposide, mitoxantrone, and cytarabine-86 trial. Archimbaud, E., Thomas, X., Leblond, V., Michallet, M., Fenaux, P., Cordonnier, C., Dreyfus, F., Troussard, X., Jaubert, J., Travade, P. J. Clin. Oncol. (1995) [Pubmed]
  18. Carcinomas of Bartholin's gland. Histogenesis and the etiological role of human papillomavirus. Felix, J.C., Cote, R.J., Kramer, E.E., Saigo, P., Goldman, G.H. Am. J. Pathol. (1993) [Pubmed]
  19. Low-risk persistent gestational trophoblastic disease: outcome after initial treatment with low-dose methotrexate and folinic acid from 1992 to 2000. McNeish, I.A., Strickland, S., Holden, L., Rustin, G.J., Foskett, M., Seckl, M.J., Newlands, E.S. J. Clin. Oncol. (2002) [Pubmed]
  20. Specificity of mouse GM2 activator protein and beta-N-acetylhexosaminidases A and B. Similarities and differences with their human counterparts in the catabolism of GM2. Yuziuk, J.A., Bertoni, C., Beccari, T., Orlacchio, A., Wu, Y.Y., Li, S.C., Li, Y.T. J. Biol. Chem. (1998) [Pubmed]
  21. Seroprevalence, correlates, and characteristics of undetected coeliac disease in England. West, J., Logan, R.F., Hill, P.G., Lloyd, A., Lewis, S., Hubbard, R., Reader, R., Holmes, G.K., Khaw, K.T. Gut (2003) [Pubmed]
  22. Electron transfer flavoprotein deficiency: functional and molecular aspects. Schiff, M., Froissart, R., Olsen, R.K., Acquaviva, C., Vianey-Saban, C. Mol. Genet. Metab. (2006) [Pubmed]
  23. Eccrine porocarcinoma (malignant eccrine poroma): a clinicopathologic study of 69 cases. Robson, A., Greene, J., Ansari, N., Kim, B., Seed, P.T., McKee, P.H., Calonje, E. Am. J. Surg. Pathol. (2001) [Pubmed]
 
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